Privileged structure based ligands for melanocortin receptors-4,4-Disubstituted piperidine derivatives

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 14, 2006, Pages 3843-3846

  Kuklish, Steven L ^a   Backer, Ryan T ^a   Briner, Karin ^a   Doecke, Christopher W ^a   Husain, Saba ^a   Mullaney, Jeffrey T ^a   Ornstein, Paul L ^a   Zgombick, John M ^a   O'Brien, Thomas P ^a   Fisher, Matthew J ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

G protein coupled receptors; GPCR; MC4; Melanocortin; Privileged structure

Indexed keywords

CARBON; CYCLOHEXANE DERIVATIVE; MELANOCORTIN 4 RECEPTOR; NITROGEN; OXYGEN; PIPERIDINE DERIVATIVE; SULFONE; SULFUR;

ARTICLE; BINDING AFFINITY; CHIRALITY; CYCLIZATION; DRUG DESIGN; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; EMBRYO; HUMAN; HUMAN CELL; LIPOPHILICITY; SUBSTITUTION REACTION;

BINDING SITES; CARBON; CYCLOHEXANES; LIGANDS; OXYGEN; PIPERAZINES; RECEPTOR, MELANOCORTIN, TYPE 4; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONES; SULFUR;

EID: 33746502556     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.04.016     Document Type: Article

References (16)

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11. 2O (5.4 mL, 1.6 mmol) (additional alkyl Grignard may be added and heated to 40 °C to drive the reaction to completion if needed. This extra effort was most commonly used for examples with structures like 7a-g). The mixture was stirred for 18 h and then poured into water (50 mL). The mixture was then partitioned between brine and EtOAc. The organic phase was then washed with brine and concentrated to dryness. Purification by column chromatography (silica gel, 9:1 chloroform/methanol), Yield: 23.6% (0.12 g).
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16. Data given are the average of at least two determinations with an average error of 15%. Biological testing was conducted on either the resulting TFA salt or the hydrochloride salt.